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Subversion of host trafficking machinery by Hepatitis C Virus to promote viral replication

Objective

Hepatitis C virus (HCV) is an important cause of worldwide liver disease. Current therapies are inadequate for most patients. Improving the understanding of the life cycle of this virus may provide opportunities for new antiviral strategies. Like all characterized positive-strand RNA viruses, HCV is also believed to replicate its RNA in association with intracellular membranes, the details of its replication complex assembly are unknown. My long-term goal is to understand the molecular mechanisms used by HCV to form its membrane-associated replication complexes. I hypothesize that in order to assemble membrane-associated replication complexes, HCV hijacks and redirects the function of components of the host’s vesicular membrane trafficking pathways. I have recently discovered such an interaction between HCV non-structural protein 5A (NS5A) and TBC1D20, a Rab1 GTPase activating protein (GAP) implicated in ER-to-Golgi transport. TBC1D20 depletion impaired HCV replication, with no affect on cell viability. Preliminary experiments reveal that TBC1D20 might also be a GAP for Arf-1, a GTPase implicated in Golgi–to-ER trafficking, suggesting an exciting model wherein NS5A’s interaction with TBC1D20 can subvert both directions of ER-Golgi transport to promote the establishment of the HCV replication complex. This project aims to further determine the role of the NS5A-TBC1D20 interaction in the establishment of the HCV replication complex and to determine the role of Arf1 in HCV replication.

Field of science

  • /medical and health sciences/health sciences/infectious disease/RNA virus
  • /social sciences/social and economic geography/transport

Call for proposal

FP7-PEOPLE-IRG-2008
See other projects for this call

Funding Scheme

MC-IRG - International Re-integration Grants (IRG)

Coordinator

TEL AVIV UNIVERSITY
Address
Ramat Aviv
69978 Tel Aviv
Israel
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 100 000
Administrative Contact
Lea Pais (Ms.)